❙ Wolfgang Domej ❙
Die Diamox-Geschichte Alles über den Carboanhydrasehemmer The Diamox-Story Everything about the carbonic anhydrase inhibitor
SUMMARY Of the few pharmacologic substances used to prevent severe acute high-altitude intolerance, the most effective and presumably the most popular is acetazolamide (ACZ/Diamox®). As a sulfonamide derivative, ACZ is a selective and reversible inhibitor of renal carboanhydrase (CA) and acts primarily to increase HCO3- excretion by the kidneys. As a mild diuretic it also increases the elimination of sodium, potassium and water due to its renal impact on the reversible hydration of carbon dioxide and dehydration of carbonic acid; this in turn moderately acidifies the plasma. ACZ has been used worldwide for more than 60 years by mountaineers, mainly to improve ventilation, nocturnal oxygen saturation and sleep. Many in this community call ACZ an “artificial acclimatizer”. Numerous placebo-controlled studies have demonstrated the effectiveness of a prophylactic dose prior to ascent to high altitude in preventing and diminishing symptoms of acute mountain sickness (AMS), e.g. morning headache, nausea, shortness of breath, fatigue, dizziness and drowsiness. Dynamic lung function tests, hypoxic ventilatory drive as well as O2-saturation are significantly better in ACZ-treated subjects susceptible to AMS as well as in asymptomatic mountaineers compared to non-treated individuals. ACZ also attenuates hypoxic pulmonary vasoconstriction (HPV) by selective inhibition of hypoxia-induced Ca2+-channels on the basis of mechanisms independent of CA inhibition, pH-value or membrane potential, so that even low-dose ACZ decreases high altitude pulmonary hypertension by lowering 25
